Ects of Herpes simplex virus HSV on DRG neuron ion channels

HSV induces a selective loss of sodium currents in DRG neurons Herpes simplex virus type 1 (HSV-1) is a common neurotropic virus that, in vivo, forms a latent infection in primary afferent neurons. HSV infection is associated with abnormal sensations around the site of initial infection including tingling, parasthesia, loss of touch and pain sensations (Andoh et al 1995) which have been FIG. 4. (Top) Na+ currents evoked by voltage steps from 80 mV to 10 mV in control (left) andHSV-infectedDRG...

Note added in proof

During the past year, several mutations responsible for epilepsy have been identified in SCN1A and SCN2A (reviewed in Meisler 2001). Baulac S, Gourfinkel-An I, Picard F et al 1999 A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet 65 1078-1085 Bulman DE 1997 Phenotype variation and newcomers in ion channel disorders. Hum Mol Genet 6 1679-1685 Caldwell JH, Schaller KL, Lasher RS, Peles E, Levinson SR 2000 Sodium channel...

Channelopathies episodic disorders of the nervous system

Howard Hughes Medical Institute, Departments of Neurology and Human Genetics, University of Utah School of Medicine, Eccles Institute of Human Genetics, Building533, Room 4425, Salt Lake City, UT 84112, USA Abstract. The field of channelopathies is a newly recognized group of disorders named after the site of their molecular defects voltage- and ligand-gated ion channels. While voltage-gated ion channel mutants have been recognized for some time in organisms such as Drosophila, the first...

Clinical manifestations

Episodic ataxia is a rare inherited syndrome of intermittent ataxia of early onset with no known inborn errors of metabolism. There are two distinct forms, both with episodic attacks of ataxia responsive to acetazolamide, with features reminiscent of periodic paralysis and suggestive of underlying ion channel abnormalities. Episodic ataxia type 1 (EA1), an autosomal dominant disorder involving both the central and the peripheral nervous system, is characterized by attacks of ataxia and...

Restricted localization of SCN5A to brain limbic pathways

In a search for genes underlying TTX-insensitive Na+ currents (White et al 1993) in brain, Hartmann et al (1999) localized the pattern of SCN5A gene expression in mammalian brain. Northern analysis of total brain RNA had failed to demonstrate expression of SCN5A mRNA. However, the more sensitive PCR amplified low levels of SCN5A cDNA from rat cortex and neonatal spinal cord (Yarowsky et al 1991, Black et al 1998). In situ hybridization and RT-PCR analysis revealed selective expression of SCN5A...

Hereditary hyperekplexia glycine receptor channel

Hereditary hyperekplexia, or startle disease, is a rare, highly penetrant autosomal dominant disorder characterized by an exaggerated startle response and hypertonia. The normal startle reflex is a primitive reflex with a complex, stereotyped pattern of motor behaviour in response to unexpected sensory stimuli. The motor response generally consists of blinking, grimacing, flexion of neck and arms, and delayed abduction of the hand muscles. Patients with startle syndromes due to various...

Periodic paralysis and nondystrophic myotonia

Periodic paralyses and nondystrophic myotonias include a number of distinct clinical entities as well as some intermediate forms of the various disorders. Myotonia congentia is a group of muscle disorders named for the prominent FIG. 3. Diagram of a subunit of nicotinic acetylcoline receptor channel or inhibitory glycine receptor channel. There are four membrane-spanning segments. These proteins are not homologous to voltage-gated channels. muscle hyperexcitability or myotonia that is seen in...

Sodium channels and epilepsy electrophysiology

Harvard Medical School and Brigham amp Women's Hospital, Longwood Medical Research Center, 221 LongwoodAve, Boston MA 02115, USA Abstract. We examined the electrophysiology of epilepsy in the simplest system that exhibits epileptiform activity microisland cultures that contain only one neuron. Some of these solitary excitatory hippocampal neurons generate the 'ictal' epileptiform activity characteristic of seizures. These neurons have endogenous non-transmitter-mediated bursts of activity that...

Molecular mechanisms of gating and drug block of sodium channels

Department ofPharmacology, University of Washington, Box 357280, Seattle, WA 98195-7280 A bstract. Voltage-gated Na channels are composed of an a subunit of260 kDa associated with b subunits of 33 36 kDa. a subunits have four homologous domains I to IV containing six transmembrane a helices S1 S6 . The S4 segments serve as voltage sensors and move outward to initiate activation. The S5 and S6 segments and the short membrane-associated loops between them form the pore. Fast inactivation is...